Age-related changes in hepatocyte function will be measured in livers of intact rats and hepatocytes in culture. Among the parameters to be evaluated are causes for the apparent decrease in protein and RNA synthesis in livers of aged rats by measuring the in vitro translation products of poly(A plus) and poly(A minus) polysomal mRNA. Similar comparisons will be made with the heterologous RNA synthesized in the nucleus and its processing to cytoplasmic mRNA. RNA-excess DNA hybridization studies should reveal whether there are differences in unique sequences transcribed from the DNA of livers from old and young rats. Also under investigation are changes associated with the chromosomal proteins and histones which might be responsible for the attendant transcriptive anomalies associated with aging. The already demonstrated alteration of transport of such compounds as a function of membrane composition will be evaluated with respect to age and time in culture of the hepatocytes. Scanning and transmission electron microscopy are planned to determine potential morphological differences between young and aged cells and cells in culture after various intervals. Additional studies are in progress to develop conditions for the maintenance of hepatocytes in culture for prolonged periods of time.